In the majority of patients with Parkinson’s disease (PD),
it is now clear that genetic factors contribute to the
pathogenesis of PD, although the contribution of genetic and
environmental factors remains to be elucidated. The contribution
of genetic factors to the pathogenesis of PD is supported by the
demonstration of the high concordance in twins, increased risk
among relatives of PD patients in case control and family
studies, and the existence of familial PD based on single gene
defects. Recently, several genes have been mapped and identified
in patients with familial PD (FPD). α-Synuclein is involved in a
rare dominant form of familial PD with dopa responsive
parkinsonian features and Lewy body positive pathology. In
contrast, parkin is
responsible for autosomal recessive form of earlyonset PD with
Lewy body-negative pathology. This form is identified with
world-wide distribution among patients with young-onset PD.
Furthermore, ubiquitin carboxy terminal
hydrolase L1 (UCHL1) gene is responsible for an
autosomal dominant form of typical PD, although only a single
family has so far been identified with a mutation of this gene.
In addition, DJ-1 has been identified as a causative gene for
PARK7, a recessive form of familial PD. Now, a total of five
causative genes including NR4A2 have been identified, and others
such as PARK3, -4, -6, -8, -9, -10 have been mapped as
hereditary forms of familial PD. The presence of different loci
or different causative genes indicates that PD is not a single
entity but a highly heterogeneous disorder. However, the
functions of causative genes may share a common pathway such as
an ubiquitin-proteasome pathway. Thus, identification and
elucidation of the causative genes should enhance our
understanding of the pathogenesis of not only familial PD, but
also sporadic PD.